tbuckley/cabot-search huggingface dataset:
Clinical benefit of imatinib in patients with relapsed tenosynovial giant cell tumor/pigmented villonodular synovitis (TGCT/PVNS).
Authors: Jeanette Cu Yu, Manpreet Kaur Sidhu, Andrew Fang, Lee Jae Morse, Minggui Pan
Journal: Journal of Clinical Oncology (2022)

e23561 Background: TGCT/PVNS is an uncommon benign but locally aggressive tumor that affects joints and can lead to significant morbidity. It is characterized in most cases by a t(1;2) translocation that leads to overexpression of colony-stimulating factor 1 (CSF-1) and the accumulation of inflammatory cells that express CSF-1 receptor (CSF-1R) in the affected joints. Imatinib inhibits the tyrosine kinase activity of CSF-1R. Methods: We retrospectively reviewed patients with TGCT/PVNS who received treatment with imatinib within Kaiser Permanente Northern California. Results: Nine patients with relapsed TGCT/PVNS were treated with imatinib from 2019 to 2022. Median age was 43 years. 6 patients were female. The imatinib dose was 400 mg daily. All patients had been treated with surgery previously and relapsed, and further surgery was considered not to be beneficial. All patients presented with persistent joint pain that affected joint mobility and walking. After imatinib therapy was initiated, 7 patients (78%) reported significant improvement in their symptoms, while 2 patients (22%) reported no significant changes. Improvement in symptoms occurred soon after starting therapy, ranging from 3 days to 5 weeks. 8 patients (89%) had stable disease by RECIST criteria based on MRI, and 1 patient was not evaluable. 5 patients are still receiving imatinib currently. The longest treatment duration is 27 months. 4 patients required a dose reduction secondary to toxicity, and 3 patients discontinued therapy (2 patients with G3/4 hepatotoxicity and 1 patient self-discontinued treatment). 2 patients who discontinued imatinib continue to experience resolution of joint pain and other symptoms 10 and 24 months later respectively. Conclusions: Our study shows that treatment with imatinib can result in rapid and lasting symptomatic improvement in patients with relapsed TGCT/PVNS, even after treatment discontinuation. This suggests that imatinib can be an effective and safe treatment option for patients with relapsed TGCT/PVNS refractory or not amenable to further surgery.
Non‐PCR Ultrasensitive Detection of Viral RNA by a Nanoprobe‐Coupling Strategy: SARS‐CoV‐2 as an Example
Authors: Zhiguo Yu, Wenming Fang, Yannan Yang, Heliang Yao, Ping Hu, Jianlin Shi
Journal: Advanced Healthcare Materials (2022)

Developing efficient and highly sensitive diagnostic techniques for early detections of pathogenic viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is vitally important for preventing its widespread. However, the conventional polymerase chain reaction (PCR)-based detection features high complexity, excessive time-consumption, and labor-intensiveness, while viral protein-based detections suffer from moderate sensitivity and specificity. Here, a non-PCR but ultrasensitive viral RNA detection strategy is reported based on a facile nanoprobe-coupling strategy without enzymatic amplification, wherein PCR-induced bias and other shortcomings are successfully circumvented. This approach endows the viral RNA detection with ultra-low background to maximum signal ratio in the linear signal amplification by using Au nanoparticles as reporters. The present strategy exhibits 100% specificity toward SARS-CoV-2 N gene, and ultrasensitive detection of as low as 52 cp mL
Mefatinib as first-line treatment of patients with advanced non–small cell lung cancer harboring rare EGFR mutations.
Authors: Pingli Wang, Liming Cao, Panwen Tian, Shengxiang Ren, Liyun Miao, Chengzhi Zhou, Yun Fan, Yuping Li, Dongqing Lv, Xin Zhao, Mei Yang, Chaonan Zhu, June Xu, Yong Song, Kai Wang
Journal: Journal of Clinical Oncology (2022)

9102 Background: Mefatinib is a novel, second-generation, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). A Phase Ib/II study has showed promising efficacy in patients with advanced EGFR (19del/L858R) mutant non-small cell lung cancer (NSCLC). This study is aimed to assess the efficacy and safety of mefatinib as first-line therapy for advanced rare EGFR mutations (G719X/S768I/L861Q) NSCLC. Methods: In this phase II study, we enrolled patients with stage IIIB-IV lung adenocarcinoma with at least one mutation in G719X, L861Q, and S768I who hadn¡¯t received front-line anticancer therapy. Other concurrent EGFR mutations were allowed with the exception of Ex19del, L858R, and exon 20 insertions. Eligible patients were treated with mefatinib 80 mg orally once daily. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 criteria. Results: A total of 21 patients (median age 57.6, 47.62% male) have been enrolled, 80.95% with G719X, 33.3% S768I, and 19.05% L861Q. Six (28.57%) patients had concurrent mutations of G719X and S768I, and one (4.76%) patient had co-mutations of G719X and L861Q. As of data cut-off (Jan, 6, 2022), median follow-up was 25.1 months. Among the 21 efficacy evaluable patients, ORR was 85.71% (95% CI, 63.66-96.95) with a duration of response (DOR) of 22.2 months (95% CI, 8.4-NA). Disease control rate (DCR) was 100% (95% CI, 83.89-100.00). Median progression-free survival (mPFS) was 20.6 months (95% CI, 8.3-NA). Median overall survival (OS) was not reached.. The most common treatment-related adverse events (TRAEs) were rash (20, 95.24%), diarrhea (19, 90.48%), stomatitis (15, 71.43%), and pandactilitis (9, 42.86%). Grade 3 TRAEs were reported in 47.63% patients. Common Grade 3 TRAEs (¡Ý5%) included diarrhea (8, 38.10%) and rash (5, 23.81%). No ¡ÝGrade 4 TRAE or treatment-related SAE reported. 33.33% (n=7) of patients experienced dose reduction due to AEs (mainly diarrhea and rash). All TRAEs were reversible and remained stable or recovered without sequelae after dose reduction. None of the patients discontinued treatment or died due to TRAE. Conclusions: Mefatinib has shown promising anti-tumor activity and a favorable safety profile in patients with advanced NSCLC harboring rare EGFR mutations. Clinical trial information: CTR20190110. [Table: see text]
Collaborative federated learning behind hospitals’ firewalls for predicting histological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.
Authors: Jean Ogier du Terrail, Armand Leopold, Clément Joly, Mathieu Andreux, Charles Maussion, Benoit Schmauch, Mikhail Zaslavskiy, Gilles Wainrib, Maud Milder, Julie Gervasoni, Julien Guérin, Thierry Durand, Alain Livartowski, Kelvin Moutet, Clément Gautier, Anne-Laure Moisson, Camille Marini, Mathieu Galtier, Pierre Etienne Heudel, Guillaume Bataillon
Journal: Journal of Clinical Oncology (2022)

590 Background: Triple-Negative Breast Cancer (TNBC) is characterized by high metastatic potential and poor prognosis with limited treatment options. Neoadjuvant chemotherapy (NACT) is the standard of care in non-metastastic setting due to the ability to assess pathologic responses providing important prognostic information and guidance in adjuvant therapy decisions. However, the histological response heterogeneity is still poorly understood. We investigate the use of Machine Learning (ML) to predict from diagnosis Whole-Slide Images (WSI) of early TNBC the positive histological Complete Response (pCR) to NACT on surgical specimens. To overcome the known biases of small scale studies while respecting data privacy, we conduct a study in a multi-centric fashion behind hospitals’ firewalls using collaborative Federated Learning (FL). Thereby allowing access to enough TNBC data to sustain a complete response heterogeneity investigation. Methods: We collected in both comprehensive cancer centers: Centre Léon Bérard (A)(n=99) and Institut Curie (B) (n=420), WSI of biopsies performed at diagnosis and relevant clinical variables. We use traditional Multiple Instance Learning pipelines by tiling the matter on each WSI with a pre-trained Neural Network (NN). We train a second NN to predict the NACT pCR using the mean feature of each WSI. ML trainings are performed using either one cohort in isolation (NN Local) or both cohorts using FL. We compare the performance of this federated WSI based model to the best clinical model (Clin.) simulating clinical practice (using grade and Tumor-Infiltrating Lymphocytes (TILs) percentage) on both centers. Results: Performance of models to predict NACT pCR (AUC). All results are evaluated in 5 repeated 4-folds cross validations. Conclusions: The final ML model, that was trained in a privacy preserving fashion on both hospitals, provides better prediction of NACT pCR than current clinical standards. This study shows that 1. Not all relevant information is routinely extracted from WSI and 2. Non simulated FL is possible in Healthcare and gives better results than siloed studies on open medical questions. Additional interpretability results of the model show that it has re-discovered known biomarkers such as TILs and apocrine tumor cells without any tile-level annotation, and hints at potential new biomarkers. [Table: see text]
Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients
Authors: Peng Xia, Xu-Dong Xing, Cui-Xian Yang, Xue-Jiao Liao, Fu-Hua Liu, Hui-Huang Huang, Chao Zhang, Jin-Wen Song, Yan-Mei Jiao, Ming Shi, Tian-Jun Jiang, Chun-Bao Zhou, Xi-Cheng Wang, Qing He, Qing-Lei Zeng, Fu-Sheng Wang, Ji-Yuan Zhang
Journal: Military Medical Research (2022)

Mucosal-associated invariant T (MAIT) cells are systemically depleted in human immunodeficiency virus type 1 (HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy (cART). This study aimed to identify the mechanism underlying MAIT cell depletion.In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D (GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12 (IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients, which could potentiate disease progression and poor immune reconstitution.
A real-world evidence of immunotherapy adoption in non-small cell lung cancer (NSCLC) treatment and its transition from platinum-refractory to the first line of therapy.
Authors: Pedro De Marchi, Pedro Nazareth Aguiar, Rafael Paes, Matheus Costa e Silva, Isabella Favato Barcelos, Gabriela Monte Tenorio Taveira, Tatiane Caldas Montella, Bruno Lemos Ferrari, Carlos H. Barrios, Carlos G. M. Ferreira, Rodrigo Dienstmann
Journal: Journal of Clinical Oncology (2022)

e18714 Background: over the past few years, multiple clinical trials have shown that immune checkpoint inhibitors (ICI) are active in NSCLC treatment. In 2015, survival improvement was demonstrated with second line immunotherapy. More recently, benefit was proven in the first line setting, both with ICI alone or in combination with chemotherapy. How fast the medical community has incorporated these advances into its clinical practice needs to be evaluated, as well as ICI efficacy in a real-world setting. Methods: retrospective analysis of the Oncoclinicas Data Lake was carried out to extract and curate information on the use of ICI in NSCLC patients from 2015 onwards, as well as survival outcomes from start of treatment to death or last follow-up. Patients with actionable driver alterations were excluded from this analysis. Results: 767 patients were identified. Median age was 72 years, 54% were male. The number of patients treated with ICI increased dramatically in the period, from 13 in 2015 to 243 in 2020. Most patients (86%) received ICI in the second line or beyond in 2015, while in 2019 and 2020 the preference was immunotherapy in the first-line setting (60%). The transition from platinum-refractory to the first line was observed for both ICI single agents and ICI combinations. As of 2021, 75% of ICI + chemotherapy treatments take place in the first line setting and 54% of ICI monotherapy treatments are given in first line setting. Overall, median overall survival was 15.7 months for first line setting use of ICI (CI 95% 12.2-19.6) and 11.6 months for second line and beyond (CI 95% 8.9-14.2). Survival rates at 12 and 24 months for first line ICI use were 56% and 48.5% and for second line and beyond 35% and 25.5%, respectively. Conclusions: ICI was promptly incorporated into the treatment of NSCLC and its use has shifted from platinum-refractory to treatment-naïve setting, mostly with combination regimens. Our cohort shows real-world overall survival rates comparable with published literature, despite a more elderly population than clinical trials.
The association of cancer diagnosis with frailty status in high need, high risk veterans.
Authors: Natasha M Resendes, Shivan M Oomrigar, Toufic Tannous, Jorge G Ruiz, Iriana M Hammel
Journal: Journal of Clinical Oncology (2022)

e24024 Background: Frailty, a common geriatric condition, is characterized by a vulnerability to stressors caused by multisystem dysfunction associated with poor clinical outcomes. Patients with frailty are often High-Need High-Risk (HNHR), a group with higher levels of healthcare utilization. Cancer diagnosis could increase the incidence of frailty in this group by several mechanisms: immunosenescence, chronic inflammation, potentially harmful effects of therapies and associated comorbidities. The study aim was to determine the cross-sectional association of cancer with frailty status in High Need, High Risk veterans. Methods: This was a cross-sectional study of HNHR Veterans in the Veterans Integrated Service Network 8 identified through quarterly reports run by VA predictive analytic models. We compared Veterans with and without cancer in terms of frailty status, sociodemographic characteristics, substance or alcohol abuse and number of medications. Frailty was defined using a 30-item VA Frailty Index (VA-FI, excluding cancer) generated as a proportion based on the number of items present. We compared non-frail (robust = 0–0.1, and pre-frail = 0.11–0.20), and frail (mild = 0.21–0.30, moderate = 0.31–0.40, and severe = &gt; 0.4). After adjusting for gender, age, alcohol abuse, tobacco abuse and number of medications, we performed a multinomial logistic regression using odds ratios (OR) with 95% confidence intervals (CI) with cancer as the independent variable and frailty status as the dependent variable. Results: A total of 10916 Veterans were included in the analysis, mean age 68.5 (SD = 11.8) years, 93.4% male, 74.7% Caucasian, 18.0% Black, 7.4% Hispanic, 8710 (79.8%) frail and 3641 (36.1%) had Cancer. Of those with cancer, frail = 3358 (85.2%) vs. non-frail = 583 (14.8%) (p &lt; .0001). After multivariate multinomial logistic regression, the presence of cancer was associated with being severely frail as compared to robust, adjusted OR:2.3(95%C.I.:1.8-2.9), p &lt; 0.0001. Conclusions: In this HNHR veteran population, cancer had a positive, cross-sectional association with frailty. Identifying HNHR patients with cancer may assist clinicians in the implementation of targeted clinical interventions that may prevent or reverse frailty status and associated poor clinical outcomes. More research is needed to better determine the impact of cancer on frailty diagnosis.
A mixed-methods study of minority patients treated on a cancer clinical trial at a tertiary referral center.
Authors: Mary O'Shea, Yonghun Kim, Gladys Asiedu, Rahma M. Warsame, Katharine Andress Rowe Price
Journal: Journal of Clinical Oncology (2022)

e18543 Background: Representation of minority patients (pts) in cancer clinical trials (CCTs) is low and contributes to health disparities. Our study sought to understand the beliefs and motivations of minority patients and to identify barriers and facilitators of CCT enrollment. Methods: 270 minority pts treated on CCT were identified from the medical record from 2018-2021. Of the 138 of pts alive, 13 (9.4%) consented. Semi-structured qualitative interviews were conducted exploring motivations, barriers, and facilitators to CCT participation. Surveys collected demographics and explored beliefs towards cancer and factors that influenced participation. Results: Of the 13 participants, 9 were female (69%), 4 Hispanic (30%), 3 Black (23%), 3 multiple races (23%), 2 Asian (15%), 2 Native American (15%), and 1 Native Hawaiian (8%). Two pts had a high school education (15%), 7 ≥ 4-year college (54%), 4 ≥ 2-year college (30%). Eight pts were married, 3 divorced, 1 widowed, and 1 single. Employment status was: employed (4 pts, 30%), unemployed (1 pt, 8%), disabled (5 pts, 38%), retired (3 pts, 23%). All pts were insured. Median household was 3 people (range 1 to &gt; 5); 3 pts had dependents. 9 pts had their own vehicle; 4 used public or subsidized transport. 2 pts had trouble finding transportation. Income was: 3 pts &lt; 25K, 4 pts 25-35K, 1 pts 35-50 K, 1 pts 50-75K, and 4 pts &gt; 75K. 4 pts received emotional support from religion. All pts had heard of CCTs and 6 (46%) had known other CT participants. Direct communication from healthcare provider was the most common way of hearing about CCT. 9 pts (69%) had trust or strong trust in experimental therapy/CCT; 4 pts (30%) were neutral. 8 pts (61%) believed standard therapy was needed to cure cancer. 5 pts (38%) believed God would decide if they die from cancer. 7 pts (54%) believed that worry makes cancer worse. Key themes about patients’ motivation to participate: chance for cure, staying positive, giving back to others, having representation in research, and advancing science. Key themes about facilitators to participation: supportive family, cost coverage for treatment, and limited treatment options. Key themes on participation: minimizing logistical barriers, decentralizing CCTs, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on purpose and benefit of CCT. Factors from survey that influenced participation are summarized in Table. Conclusions: Understanding minority pts experience through in-depth interviews is valuable and may help with recruitment.[Table: see text]
Salvage high-dose chemotherapy (HDCT) for relapsed primary mediastinal nonseminomatous germ-cell tumors (PMNSGCT).
Authors: Fadi Taza, Rafat Abonour, Sandra K. Althouse, Ryan Ashkar, Mohammad Issam Abu Zaid, Nasser H. Hanna, Kenneth A. Kessler, Nabil Adra, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2022)

5032 Background: Patients with PMNSGCT have high relapse rates after first-line therapy. Historical outcomes in this subset with standard-dose salvage chemotherapy or HDCT+bone marrow transplant (BMT) have been poor. The use of peripheral-blood stem-cell transplant (PBSCT) has allowed for more rapid engraftment and the ability to start the 2 nd course 3-4 weeks after the 1 st course of HDCT. We report survival outcomes of salvage HDCT+PBSCT in relapsed PMNSGCT. Methods: Between 2004-January 2021, 32 pts with relapsed PMNSGCT were treated with HDCT+PBSCTx2 utilizing our institutional regimen: carboplatin 700 mg/m2 + etoposide 750 mg/m2, for 3 consecutive days, followed by PBSCT. Median time between cycle1 day1 to cycle2 day1 was 3.2 wks (range, 2.6-4.6). Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) analysis. Results: Median age was 30. At the start of HDCT, median AFP was 192 (range, 4-17130) and hCG 1.5 (range, 0.6-15711). First-line therapy was standard germ cell tumor chemotherapy such as bleomycin-etoposide-cisplatin (BEP) or etoposide-ifosfamide-cisplatin (VIP). HDCT was 2nd line in (26, 81.3%) and 3rd line in (6, 18.8%). Eighteen (56.3%) pts had platinum-refractory disease defined as progression within 4 weeks of 1st line chemo. Twenty-three (72%) patients had extra mediastinal metastases (mets) at the start of HDCT. Metastatic sites included pulmonary (17), lymph nodes (2), liver (3), bone (2), brain (1). Median follow-up time from start of HDCT was 1 yr (range, 0.02-14.1). Twenty-six (81%) pts completed both cycles, while 6 (19%) completed only one cycle due to toxicity or progression. The estimated 2-yr PFS was 30.7 (95% CI, 15.8-46.9) and 2-yr OS was 35.2 (95% CI, 18.9-51.9). At the most recent follow-up, 9 (28%) pts were continuously no evidence of disease (NED), including 2 pts who had surgical resection of teratoma following HDCT. Median follow-up from the start of HDCT for the NED pts was 4.6 yrs (range, 1-14.1). Five of the NED pts had extra mediastinal mets, and 2 had platinum-refractory disease. Among the 9 NED pts, HDCT was 2nd line in 7 (77.8%) and 3rd line in 2 (22.2%). These results compare favorably to historical data with standard-dose chemotherapy or HDCT+BMT in relapsed primary mediastinal GCT with salvage rates &lt; 10% (Hartmann et al., JCO 19:1641-1648, 2001). Grade ≥3 toxicity, as previously described in our study (Adra et al., JCO 35:1096-1102, 2017), occurred in 8 (25%) pts. There were two treatment-related deaths. Conclusions: HDCT+PBSCT is a safe and effective salvage therapy in pts with relapsed PMNSGCT with curative potential. In our opinion, these complicated patients are best managed at tertiary centers with expertise in medical oncology, stem cell transplantation, and thoracic surgical oncology.
Medical Device User Fee Reauthorization — Back to Basics or Looking Ahead?
Authors: Vinay K. Rathi, Joseph S. Ross, Rita F. Redberg, Sanket S. Dhruva
Journal: New England Journal of Medicine (2022)

Interview with Dr. Vinay Rathi on the medical device user-fee program and strategies for supporting device safety and innovation. (10:49)Download User fees are vital to FDA operations. But user-fee legislation has focused on expediting premarketing review rather than understanding device risks and benefits throughout the product life cycle.